- E-cadherin, or epithelial cadherin, is a transmembrane glycoprotein that plays a fundamental role in maintaining the structure and integrity of epithelial tissues. It is a key component of adherens junctions, where it mediates calcium-dependent cell-cell adhesion, ensuring tight intercellular contact and epithelial polarity. During epithelial-to-mesenchymal transition (EMT), E-cadherin is one of the most consistently downregulated markers, making its loss a hallmark of this process. The reduction or loss of E-cadherin function is crucial for allowing epithelial cells to detach from their neighbors, acquire motility, and adopt a mesenchymal phenotype.
- The downregulation of E-cadherin is largely governed at the transcriptional level by EMT-inducing transcription factors, including Snail, Slug, Twist, and ZEB1, which bind to E-box sequences in the E-cadherin promoter and suppress its expression. In some contexts, E-cadherin can also be cleaved proteolytically by enzymes like MMP-3, further contributing to the disassembly of epithelial junctions. Functionally, the loss of E-cadherin weakens cell cohesion and promotes the cytoskeletal rearrangements and morphological changes characteristic of mesenchymal cells.
- In pathological contexts, such as cancer, fibrosis, and chronic inflammation, reduced E-cadherin levels are associated with increased cell migration, invasion, and resistance to apoptosis—features that enhance metastatic potential and disease progression. In gastric epithelial cells, for example, Helicobacter pylori infection and its virulence factor CagA have been shown to disrupt E-cadherin expression or localization, thereby facilitating EMT and tumorigenic transformation.
- Because of its central role in maintaining the epithelial phenotype, E-cadherin serves not only as a key functional regulator of EMT but also as a reliable biomarker for assessing the extent to which epithelial cells have undergone transition toward a mesenchymal state.
